Rivaroxaban versus Warfarin in Patients with Mechanical Heart Valve: Rationale and Design of the RIWA Study.

INTRODUCTION: Mechanical heart valves (MHV) are extremely durable, but they require permanent use of anticoagulation to prevent thromboembolic events. The only approved therapeutic options are vitamin K antagonists (VKAs), such as warfarin. As a drug class, clinical management is difficult, therefore new alternatives need to be evaluated. METHODS: RIWA is a phase II/III, prospective, open-label, randomized, pilot study designed to investigate oral rivaroxaban 15 mg twice daily compared with dose-adjusted warfarin for the prevention of stroke (ischemic or hemorrhagic) and systemic embolism in patients with MHV, from August 2018 to December 2019. Patients will undergo transesophageal echocardiography at the beginning and the end of the study (follow-up time 90 days). On an explanatory basis, all events will be analyzed, including stroke, peripheral systemic embolism, valve thrombosis, significant bleeding and death. DISCUSSION: Warfarin and similar VKAs are standard therapy for patients with an MHV. Even with the appropriate use of therapy, the incidence of thromboembolic events is high at 1-4% per year. Furthermore, bleeding risk is significant, ranging from 2 to 9% per year. The new frontier to be overcome in relation to use of the new oral anticoagulants is undoubtedly in patients with MHV. A significant portion of people with MHV worldwide will benefit if noninferiority of these new agents is confirmed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03566303. Recruitment Status: Recruiting. First Posted: 25 June 2018. Last Update Posted: 25 June 2018.

Cathepsin B inhibition attenuates cardiovascular pathology in mucopolysaccharidosis I mice.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder with multisystemic features, including heart enlargement, heart valve dysfunction, and aortic stiffness and dilatation. Previous studies have shown that MPS I mice overexpress cathepsin B (CtsB) in multiple tissues, including those from the cardiovascular system. Here, we hypothesized that inhibition of CtsB could ameliorate cardiac function parameters, as well as aorta and valve abnormalities found in MPS I. First, we found that total elastase activity in an MPS I aorta is elevated. Following that, we demonstrated that CtsB leaks from the lysosome in MPS I human fibroblasts, possibly acting as a degradative agent of extracellular matrix components from the aorta, cardiac muscle, and heart valves. We then used a CtsB inhibitor in vivo in the MPS I mouse model. After 4 months of treatment, partial inhibition of CtsB activity in treated mice reduced aortic dilatation, as well as heart valve thickening, and led to improvements in cardiac function parameters, although none of these were completely normalized. Based on these results, we conclude that lysosomal alterations in this disease promote leakage of CtsB to outside the organelle, where this protein can have multiple pathological roles. CtsB inhibition improved cardiovascular parameters in MPS I mice and can have a potential benefit in this disease.

Aortic and tricuspid endocarditis in hemodialysis patient with systemic and pulmonary embolism.

This is a case report of a 43-year-old Caucasian male with end-stage renal disease being treated with hemodialysis and infective endocarditis in the aortic and tricuspid valves. The clinical presentation was dominated by neurologic impairment with cerebral embolism and hemorrhagic components. A thoracoabdominal computerized tomography scan revealed septic pulmonary embolus. The patient underwent empirical antibiotherapy with ceftriaxone, gentamicin and vancomycin, and the therapy was changed to flucloxacilin and gentamicin after the isolation of S. aureus in blood cultures. The multidisciplinary team determined that the patient should undergo valve replacement after the stabilization of the intracranial hemorrhage; however, on the 8th day of hospitalization, the patient entered cardiac arrest due to a massive septic pulmonary embolism and died. Despite the risk of aggravation of the hemorrhagic cerebral lesion, early surgical intervention should be considered in high-risk patients.

Endocardite aórtica e tricúspide em pacientes de hemodiálise com embolia sistêmica e pulmonar / Aortic and tricuspid endocarditis in hemodialysis patient with systemic and pulmonary embolism

RESUMO Este artigo relata o caso de um homem caucasiano de 43 anos de idade com nefropatia terminal em tratamento com hemodiálise e apresentando endocardite infecciosa das válvulas aórtica e tricúspide. O quadro clínico foi dominado pelo comprometimento neurológico, devido à embolia cerebral e a componentes hemorrágicos. Uma tomografia computadorizada tóraco-abdominal revelou um êmbolo séptico pulmonar. O paciente foi submetido à antibioticoterapia empírica utilizando ceftriaxona, gentamicina e vancomicina, sendo o tratamento modificado para flucloxacilina e gentamicina após o isolamento de S. aureus nas hemoculturas. A equipe multidisciplinar determinou que o paciente deveria ser submetido à substituição de válvulas após estabilização da hemorragia intracraniana; contudo, no oitavo dia após a hospitalização, o paciente entrou em parada cardíaca causada por embolia séptica pulmonar maciça, vindo a falecer. Apesar do risco de agravamento da lesão hemorrágica cerebral, em pacientes de alto risco deveria ser considerado realizar precocemente uma intervenção cirúrgica.

ABSTRACT This is a case report of a 43-year-old Caucasian male with end-stage renal disease being treated with hemodialysis and infective endocarditis in the aortic and tricuspid valves. The clinical presentation was dominated by neurologic impairment with cerebral embolism and hemorrhagic components. A thoracoabdominal computerized tomography scan revealed septic pulmonary embolus. The patient underwent empirical antibiotherapy with ceftriaxone, gentamicin and vancomycin, and the therapy was changed to flucloxacilin and gentamicin after the isolation of S. aureus in blood cultures. The multidisciplinary team determined that the patient should undergo valve replacement after the stabilization of the intracranial hemorrhage; however, on the 8th day of hospitalization, the patient entered cardiac arrest due to a massive septic pulmonary embolism and died. Despite the risk of aggravation of the hemorrhagic cerebral lesion, early surgical intervention should be considered in high-risk patients.

[Thrombolysis in left mechanical prosthetic heart valve obstruction by thrombus. Following and results]. / Trombólisis en la válvula mecánica cardiaca izquierda obstruida. Seguimiento y resultados.

BACKGROUND: Obstruction of the left mechanical heart valve by a thrombus is a serious complication. The factors associated with mortality are functional class, type of valve prosthesis and emergency surgery. Thrombolysis represents a therapeutic option to cardiac surgery. The aim of this investigation was to analyze the role of thrombolysis in the management of thrombus-obstructed left mechanical heart valve. METHODS: Twenty-two consecutive cases undergoing thrombolysis at the Cardiology Hospital of the Siglo XXI National Medical Center were studied under two different circumstances: with acute pulmonary edema and state of shock in functional class IV and with functional class I-II. Clinical and echocardiographic monitoring and fluoroscopy were performed. RESULTS: The response was satisfactory in 56 % of the patients and there were complications in 69 % of the cases. During the follow-up, recurrence of symptoms occurred in 25 % of the patients, 5-year actuarial survival in 75 % and thromboembolic events-free survival in 37 %. Mortality was 12 %. CONCLUSIONS: Thrombolysis is a management alternative in patients with thrombus-obstructed left mechanical heart valve; however, this therapeutic option must be choosen according to clinical circumstances and echocardiographic, hemodynamic or fluoroscopic findings in the patients.

INTRODUCCIÓN: la obstrucción de la válvula mecánica cardiaca izquierda por trombo es una complicación grave. Los factores relacionados con la mortalidad son clase funcional, tipo de prótesis valvular y urgencia de la cirugía. La trombólisis representa una opción terapéutica a la cirugía cardiaca. El objetivo de esta investigación fue analizar el papel de la trombólisis en el manejo de la válvula mecánica cardiaca izquierda obstruida por trombo. MÉTODOS: se estudiaron 22 casos consecutivos sometidos a trombólisis en el Hospital de Cardiología del Centro Médico Nacional Siglo XXI, bajo dos diferentes circunstancias: con edema agudo pulmonar y estado de choque en clase funcional IV y con clases funcionales I y II. Se realizó monitoreo clínico, ecocardiográfico y fluoroscopia. RESULTADOS: la respuesta fue satisfactoria en 56 % de los pacientes y hubo complicaciones en 69 % de los casos. Durante el seguimiento, la recurrencia de síntomas se presentó en 25 % de los pacientes, la supervivencia actuarial a cinco años en 75 % y la supervivencia libre de eventos tromboembólicos en 37 %. La mortalidad fue de 12 %. CONCLUSIONES: la trombólisis constituye una alternativa de manejo en los pacientes con una válvula mecánica cardiaca izquierda obstruida por un trombo, sin embargo, esta opción terapéutica debe ser elegida de acuerdo con las circunstancias clínicas, hallazgos ecocardiográficos, hemodinámicos o fluoroscópicos de los pacientes.

Anticoagulação na insuficiência cardíaca e valvopatias / Anticoagulation in heart failure and valvulopathies

A insuficiência cardíaca e as valvopatias são entidades patológicas representativas de expressiva parte do universo das cardiopatia sem nosso meio. No curso de sua evolução, têm como denominador comum o risco de desenvolvimento de eventos tromboembólicos,responsáveis muitas vezes por graves sequelas neurológicas. Os mecanismos descritos por Virchov (hipercoagulabilidade, estase, e alteração da função do endotélio - parede vascular) estão presentes nestes pacientes e explicam a maior incidência desses eventos. Embora a compreensão do risco seja algo claro na literatura atual, menos claro é o real benefício da anticoagulação e ou antiagregação plaquetária para prevenção dos eventos tromboembólicos nessa população. Particularmente na presença de fibrilação atrial, ambas as entidades expõem os pacientes ao risco de fenômenos embólicos. Na eventual presença de próteses valvares, este risco pode ser ainda superior. A opção por uma terapia anticoagulante para a prevenção de um evento trombótico ou embólico deve ser baseada na avaliação particular do risco de um paciente e nos possíveis benefícios que a anticoagulação pode oferecer. Portanto, a prevenção do tromboembolismo deve fazer parte do manejo dos pacientes portadores de insuficiência cardíaca e doença valvar. Nesse artigo, procuramos revisar sumariamente aspectos epidemiológicos e os mecanismos envolvidos na gênese do risco trombótico desses pacientes e buscamos com base em estudos clínicos relevantes, meta-análises, revisões de literatura e diretrizes vigentes, identificar as situações de benefício da terapia antitrombóticanos pacientes com IC e valvopatias.

Heart failure (HF) and cardiac valvular disease are majorrepresentatives of the pathological cardiovascular diseases. In thenatural course of these diseases, they share a major denominator,the risk of thromboembolism, which in turn are responsible forsevere neurological damage. The mechanisms described by Virchov(hypercoagulability, stasis and alteration of the endotheliumfunction - the vascular wall) are present in these patients and explainthe higher incidence of these events. Although the understandingof the risk of thromboembolism is clear in the literature, it is notwell known the real benefit of anticoagulation and/or antiplatelettherapy for the prevention of thromboembolic events in patients atrisk. Particularly, in the presence of atrial fibrillation, both entitiesexpose these individuals to the risk of severe thromboembolism.When valvular prosthesis are present, this risk can be increasedseveral times. The choice of the best regimen of the anticoagulantand antiplatelet therapies to the prevention of thromboembolismshould be based in the individual risk of patients and in the possiblebenefits offered by the anticoagulation. As both heart failure andcardiac valvular diseases share the necessity of anticoagulation,this article reviews the epidemiology and mechanisms involved inthe genesis of thrombotic risk in these patients. Relevant clinicaltrials, meta-analysis, literature reviews and current guidelines arethe foundation to identify the benefits of antithrombotic therapy inthis population.

Comparison of surgical cut and sew versus radiofrequency pulmonary veins isolation for chronic permanent atrial fibrillation: a randomized study.

BACKGROUND: Surgical pulmonary veins isolation (PVI) is done to restore sinus rhythm (SR) in patients with chronic permanent atrial fibrillation (CPAF) and mitral valve disease. Here we compare the efficacy of electrical block lines performed with radiofrequency (RF) compared with conventional surgery. METHODS: Randomized trial of 22 patients with CPAF and indication for mitral valve surgery. Ten patients underwent conventional surgery (SURG) and 12 RF. To prove the efficacy of the blockage lines, epicardial pacemaker wires were placed in the isolated pulmonary veins region (IPVR) and right atria (RA). RESULTS: There were no differences in the baseline data among the groups. All patients remained in SR during the immediate postoperative period. Block lines were tested in patients who remained in SR during the following days (eight in SURG and nine in RF). The median value of thresholds to conduct the stimulus of IPVR for the RA was 18 mA in SURG and 3 mA in RF (P < 0.022). Eight SURG patients and seven RF patients (P < 0.38) remained in SR at hospital discharge. Eleven RF patients and one SURG required amiodarone to maintain SR (P < 0.001). The incidence of recurrent atrial fibrillation (AF) in the follow-up was 10.7/100 patients/year in the SURG group versus 73.1/100 patients/year in the RF group (P = 0.009). CONCLUSIONS: PVI by SURG formed more effective block lines than RF. SR at hospital discharge was similar among the groups, but more amiodarone was used in RF. During follow-up, incidence of recurrent AF was higher in the RF group.

Uso crônico de anticoagulante oral: implicações para o controle de níveis adequados / Constant use of oral anticoagulants: implications in the control of their adequate levels / Uso crónico de anticoagulante oral implicaciones para el control de niveles adecuados

FUNDAMENTO: Dosagens inapropriadas e subterapêuticas anticoagulantes podem resultar em sérias complicações tromboembólicas. O uso dessa terapêutica requer especial atenção e precisa de um acompanhamento clínico e laboratorial rigoroso. OBJETIVO: Identificar fatores associados ao controle adequado dos níveis de anticoagulação oral, verificando o conhecimento e a percepção dos pacientes relacionados à terapêutica empregada. MÉTODOS: Estudo transversal que incluiu 140 pacientes acompanhados no ambulatório de anticoagulação oral, de novembro de 2005 a junho de 2006. Um questionário estruturado foi elaborado e aplicado para obtenção de características clínicas, conhecimento sobre a terapêutica, adesão ao tratamento (teste de Morisky) e percepção do paciente. RESULTADOS: As principais indicações para uso do anticoagulação oral foram fibrilação atrial (61,4 por cento) e prótese metálica (55 por cento). O tempo de uso variou entre 24 e 72 meses, e o femprocumona (58 por cento) foi o mais empregado. Em relaçãoà percepção da terapêutica, 95 por cento dos pacientes mencionaram preocupação com o uso diário dessa medicação. A realização periódica de exames de sangue (21,4 por cento) e a tomada rigorosa de anticoagulação oral (12,8 por cento) foram compreendidas como limitantes. Observou-se conhecimento adequado entre os pacientes com international normalized ratio (INR) fora da faixa (64 por cento) e na aderência entre os pacientes com INR dentro da faixa terapêutica (54 por cento), porém sem significância estatística. CONCLUSÃO: Os resultados deste estudo demonstraram uma prevalência de pacientes em uso de anticoagulação oral com o INR dentro dos valores ideais, embora tenha sido grande a porcentagem de pacientes não-aderentes à terapêutica. O conhecimento insatisfatório quanto à terapêutica empregada e ao autocuidado torna-se evidente nessa população.

BACKGROUND: Inappropriate and subtherapeutic anticoagulants dosages may result in severe thromboembolic and bleeding complications. The use of this treatment requires special attention and strict clinical and laboratory follow-up. OBJECTIVE: To identify factors associated with appropriate control of the oral anticoagulant use, assessing the patients' knowledge and perception of the treatment. METHODS: A cross-sectional study which included 140 patients followed in the oral anticoagulation outpatient clinic from November 2005 to June 2006. A structured questionnaire was drafted and applied to obtain the clinical characteristics of the patients and their knowledge about the treatment, their compliance with the treatment (Morisky´s test) and their perception of the treatment. RESULTS: The main indications for the use of oral anticoagulation therapy were atrial fibrillation (61.4 percent) and a prosthetic heart valve (55 percent). The duration of anticoagulation ranged from 24 to 72 months, and phenprocoumon (58 percent) was the most commonly used anticoagulant. As to the perception of the treatment, 95 percent of the patients mentioned concern about daily use of this medication. Periodic blood tests (21.4 percent) and the strict intake of oral anticoagulant (12.8 percent) were considered limiting factors. Adequate knowledge was outstanding in patients with an international normalized ratio (INR) outside the therapeutic range (64 percent), compared to patients with an INR within the therapeutic range (62 percent), as well as compliance with treatment in patients with an INR within the therapeutic range (54 percent), but with no statistical significance. CONCLUSION: The results of this study show a prevalence of patients using oral anticoagulant with an INR within optimal values, although a high percentage of patients do not comply with the treatment. In this population it is clearly seen that they do not fully understand the treatment.

FUNDAMENTO: Dosis inapropiadas y subterapéuticas anticoagulantes pueden resultar en serias complicaciones tromboembólicas. El uso de esta terapéutica requiere especial atención y precisa un seguimiento clínico y analítico riguroso. OBJETIVO: Identificar factores asociados al control adecuado de los niveles de anticoagulación oral, verificando el conocimiento y la percepción de los pacientes relacionados a la terapéutica empleada. MÉTODOS: Estudio transversal que incluyó a 140 pacientes seguidos en el ambulatorio de anticoagulación oral, desde noviembre de 2005 a junio de 2006. Se elaboró y se aplicó un cuestionario estructurado para la obtención de características clínicas, conocimiento sobre la terapéutica, adhesión al tratamiento (test de Morisky) y percepción del paciente. RESULTADOS: Las principales indicaciones para uso de anticoagulación oral fueron fibrilación atrial (61,4 por ciento) y prótesis metálica (55 por ciento). El tiempo de uso varió entre 24 y 72 meses, y el fenprocumona (58 por ciento) fue el más empleado. Con relación a la percepción de la terapéutica, el 95 por ciento de los pacientes mencionaron preocupación con el uso diario de esta medicación. La realización periódica de análisis de sangre (21,4 por ciento) y el tomar anticoagulación oral rigurosamente (12,8 por ciento) fueron comprendidos como limitantes. Se observó conocimiento adecuado entre los pacientes con international normalized ratio (INR) fuera del intervalo (64 por ciento) y en la adhesión entre los pacientes con INR dentro del intervalo terapéutico (54 por ciento), aunque sin significancia estadística. CONCLUSIÓN: Los resultados de este estudio mostraron una prevalencia de pacientes en uso de anticoagulación oral con el INR dentro de los valores ideales, aunque haya sido grande el porcentaje de pacientes no adheridos a la terapéutica. El conocimiento insatisfactorio con relación a la terapéutica empleada y al autocuidado se vuelve evidente en esa población.

Constant use of oral anticoagulants: implications in the control of their adequate levels.

BACKGROUND: Inappropriate and subtherapeutic anticoagulants dosages may result in severe thromboembolic and bleeding complications. The use of this treatment requires special attention and strict clinical and laboratory follow-up. OBJECTIVE: To identify factors associated with appropriate control of the oral anticoagulant use, assessing the patients' knowledge and perception of the treatment. METHODS: A cross-sectional study which included 140 patients followed in the oral anticoagulation outpatient clinic from November 2005 to June 2006. A structured questionnaire was drafted and applied to obtain the clinical characteristics of the patients and their knowledge about the treatment, their compliance with the treatment (Morisky s test) and their perception of the treatment. RESULTS: The main indications for the use of oral anticoagulation therapy were atrial fibrillation (61.4%) and a prosthetic heart valve (55%). The duration of anticoagulation ranged from 24 to 72 months, and phenprocoumon (58%) was the most commonly used anticoagulant. As to the perception of the treatment, 95% of the patients mentioned concern about daily use of this medication. Periodic blood tests (21.4%) and the strict intake of oral anticoagulant (12.8%) were considered limiting factors. Adequate knowledge was outstanding in patients with an international normalized ratio (INR) outside the therapeutic range (64%), compared to patients with an INR within the therapeutic range (62%), as well as compliance with treatment in patients with an INR within the therapeutic range (54%), but with no statistical significance. CONCLUSION: The results of this study show a prevalence of patients using oral anticoagulant with an INR within optimal values, although a high percentage of patients do not comply with the treatment. In this population it is clearly seen that they do not fully understand the treatment.

Fibrinolytic therapy in left side-prosthetic valve acute thrombosis. In depth systematic review.

BACKGROUND: Limited data are available on the impact and safety of fibrinolytic therapy (FT) in left - side prosthetic valve acute thrombosis (PVAT). STUDY OBJECTIVE: To improve our knowledge about the FT role in left -side PVAT. DESIGN: Bibliographic search and analysis. METHODS: MEDLINE search from January 1970 to January 2007. Studies were classified according to the evidence level recommendations of the American College of Chest Physicians and included if they had objective diagnosis of left-side PAVT and FT efficacy assessment (hemodynamic, echocardiographic or fluoroscopic improvement). New York Heart Association class was used to establish functional state. Data on clinical characteristics, diagnosis strategy, anticoagulation status, fibrinolytic and heparin regimens, cardiovascular adverse events, outcome, and follow-up were also required. RESULTS: A systematic search produced a total of 900 references. Each abstract was analyzed according to the predetermined criteria. Thirty-two references with 904 patients constitute the subject of this analysis. Only one trial had evidence III and thirty-one evidence V. FT was more used in young female patients (64%) with prosthetic mitral valve thrombosis (77%), and clinical instability (82%). Transesophageal echocardiogram had a higher thrombus detection rate (100%). Although several fibrinolytic regimens were used in a first or second course, streptokinase was the most frequent agent (61%). Clinical improvement was observed in 86% of the patients, objective success in 78%, and failure in 14%. Rescue fibrinolysis was done in 17%. COMPLICATIONS: peripheral and cerebral embolism rate was 5% and 4%, respectively. Major bleeding 4% and intracranial hemorrhage 1%. CONCLUSIONS: The available evidence demonstrates that in PVAT fibrinolytic therapy improves the outcome in younger, more ill patients, especially females, independently of the fibrinolytic regimen used with a low complications rate.

Valvular heart disease in pregnancy: a review of the literature.

The population of pregnant women with valvular heart disease represents a unique patient group with increased risk for adverse outcomes. The significant hemodynamic changes that occur during pregnancy can mimic symptoms of congestive heart failure. Furthermore, many patients with valvular heart disease are first recognized during pregnancy. Pre-pregnancy intervention is of utmost importance in high-risk women who present for evaluation before a planned pregnancy. This is more so if the valvular lesion is amenable for percutaneous intervention or repair, without replacement. Besides management during the antepartal period, timing and mode of delivery should be decided upon jointly by the obstetrician, cardiologist, and obstetric anesthesiologist. Prosthetic mechanical valves which require anticoagulation present a high risk subset of patients. The American Heart Association/American College of Cardiology Task Force recommends continuous therapeutic anticoagulation with frequent monitoring. Warfarin and Heparin have been recommended. Low molecular weight heparin is not recommended to be administered to pregnant patients with mechanical prosthetic valves unless anti-Xa levels are monitored 4 to 6 h after administration. Aspirin at low doses, 81-325 mg has been proposed to reduce the risk of thrombosis. At this moment, optimal antithrombotic therapy in pregnant women with mechanical valves cannot be definitively recommended due to lack of properly designed studies.